6-43278646-T-C

Variant names:

• chr6-43278646-T-C
• rs2756173
• NM_032538.3:c.1987-4081T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_032538.3(TTBK1):​c.1987-4081T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.484 in 152,106 control chromosomes in the GnomAD database, including 20,866 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.48 (20866 hom., cov: 33)
• Consequence: TTBK1 NM_032538.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.678
• Publications: 4 publications found

Genes affected

TTBK1 (HGNC:19140): (tau tubulin kinase 1) Summary:This gene belongs to the casein kinase 1 superfamily. The encoded protein is a neuron-specific, serine/threonine and tyrosine kinase, which regulates phosphorylation of tau, a protein that associates with microtubule assemblies and stabilizes them. Genetic variants in this gene are associated with Alzheimer's disease. [provided by RefSeq, Jul 2016]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.792 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TTBK1	NM_032538.3	c.1987-4081T>C		intron_variant	Intron 13 of 14	ENST00000259750.9	NP_115927.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TTBK1	ENST00000259750.9	c.1987-4081T>C		intron_variant	Intron 13 of 14	1	NM_032538.3	ENSP00000259750.4

Frequencies

GnomAD3 genomes AF: 0.484 AC: 73561 AN: 151988 Hom.: 20821 Cov.: 33

Gnomad AFR AF: 0.799

Gnomad AMI AF: 0.248

Gnomad AMR AF: 0.410

Gnomad ASJ AF: 0.260

Gnomad EAS AF: 0.471

Gnomad SAS AF: 0.389

Gnomad FIN AF: 0.343

Gnomad MID AF: 0.339

Gnomad NFE AF: 0.355

Gnomad OTH AF: 0.437

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.484 AC: 73662 AN: 152106 Hom.: 20866 Cov.: 33 AF XY: 0.480 AC XY: 35663 AN XY: 74348

African (AFR) AF: 0.799 AC: 33148 AN: 41486

American (AMR) AF: 0.409 AC: 6258 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.260 AC: 903 AN: 3470

East Asian (EAS) AF: 0.471 AC: 2436 AN: 5176

South Asian (SAS) AF: 0.389 AC: 1876 AN: 4822

European-Finnish (FIN) AF: 0.343 AC: 3628 AN: 10570

Middle Eastern (MID) AF: 0.357 AC: 105 AN: 294

European-Non Finnish (NFE) AF: 0.355 AC: 24168 AN: 67984

Other (OTH) AF: 0.434 AC: 915 AN: 2110

Alfa AF: 0.461 Hom.: 3583

Bravo AF: 0.502

Asia WGS AF: 0.415 AC: 1442 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.2
DANN	Benign	0.37
PhyloP100		-0.68
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2756173; hg19: chr6-43246384;